Biochemistry & Analytical Biochemistry

Abstract

How Human Alpha-lactalbumin Recognize DNA and RNA

Nevinsky GA, Alinovskaya LI, Ivanisenko NV, Soboleva SE and Sedykh SE

Human α-lactalbumin (LA) has an important function in mammary cells, activates the caspases involving in apoptosis. LA complex interacts with DNA in tumor cells with histones and impaired the chromatin structure. There are no any data on how LA recognizes DNA and interact with histones and DNA of chromatin. The approach of stepwise increase in ligand complexity was used for estimation of the relative contribution of every DNA nucleotide unit to its total affinity for human LA. It was shown that the LA DNA-binding site minimal ligands are orthophosphate and all dNMPs and rNMPs (Kd=(5.0-43)×10-5). Maximal contribution to the total affinity was observed for three nucleotide units of all (pN)n with a significant decrease in the order 1>2>3, at n=4-6 it was remarkably lower and at n ≥ 6-7 all dependencies of -logKd upon n reached plateaus. Double-stranded (pN)n showed significantly lower affinity comparing with singlestranded ligands. The thermodynamic parameters characterizing the specific contribution of (pN)1-6 every nucleotide link (ΔGo) to their total affinity for LA were estimated. The spatial model of LA-DNA complex was calculated. LA protein sequence has homology with those of five histones (H1-H4) involved in the chromatin nucleus interactions between themselves and their complex with DNA. It is assumed that the homology may be the main reason for the interaction of LA with chromatin DNA, leading to a breakdown in its structure, as well as the proper binding of histones between themselves and with DNA.